With 1/3 of the US adult population obese, the medical cost of obesity is $147 billion dollars per year. Exercise is one of the major lifestyle changes recommended to lose weight. To lose significant weight, the American College of Sports Medicine recommends >250 minutes of exercise per week. Exercise will increase body temperature, especially when it is performed at a high intensity or in the heat. Increased body temperature, or hyperthermia, leads to sweating and dehydration. Dehydration and hyperthermia increase physiological and psychological fatigue, both of which can cause premature exercise fatigue resulting in exercise cessation during the acute exercise bout as well as reduce motivation to continue a life-long exercise regimen. This failure to exercise will be counterproductive to weight loss goals and the cardiovascular benefits of exercise. Despite obesity often cited as a contributing factor to hyperthermia and heat illnesses, findings from laboratory studies investigating thermoregulatory control in obese individuals are mixed, likely because these studies did not take into consideration differences in heat generation during exercise between obese and non-obese groups. The primary objective of this project is to examine the effects of obesity on thermoregulatory control to exercise in the heat. Specific Aim 1 will test the hypothesis that overall thermoregulatory responses to exercise in the heat when euhydrated will be impaired in obese compared to non-obese individuals. Sweat rate, intestinal temperature, skin blood flow, cardiac output, stroke volume, heart rate, and blood pressure will be measured while both groups perform prolonged exercise at equal levels of oxygen uptake, and thus equal heat production. Subjects will begin and remain euhydrated throughout exercise. Specific Aim 2 will test the hypothesis that dehydration has a greater adverse effect on thermoregulatory function in obese versus non-obese individuals. The same measures will be obtained as Aim 1 while subjects undergo the same exercise protocol. However, prior to testing, subjects will be 3% dehydrated (i.e., reduction of 3% body mass) by performing an exercise and heat exposure. Specific Aim 3 will identify mechanisms responsible for modified thermoregulatory responses in obese individuals. Specifically, we will identify the mechanisms responsible for attenuated skin blood flow and increased local sweat rate responses in obese individuals while euhydratad. These questions will be answered by performing a series of mechanistic studies using subcutaneous microdialysis membranes and administration of local vasodilators (nitric oxide donor and acetylcholine) and sweat gland stimulates (acetylcholine).The information gained from the proposed project will provide valuable data to aid in understanding the effects of obesity on exercise thermoregulation and could alter fluid replacement and exercise recommendations for obese individuals. PUBLIC HEALTH RELEVANCE: Although population studies suggest that obese individuals, compared to their lean counterparts, are at an increased risk for high body temperature, there is very little scientific data to support the public and scientific belief that obese individuals "store heat" or heat up quicker when exercising. In order to promote public health and the loss of weight for the 72 million obese Americans, it is imperative that the scientific community understands the precise magnitude and mechanisms of cardiovascular and body temperature control in obese individuals. The proposed project will identify how obese individuals control body temperature while exercising and will provide insight into understanding a previously unidentified barrier for obese individuals to achieve the degree of exercise stimulus needed to decrease body weight.